tbuckley/cabot-search huggingface dataset:
RADT-25. UNDERSTANDING PATTERNS OF TUMOUR INFILTRATION IN PATIENTS WITH MULTIFOCAL GLIOBLASTOMA AND IMPACT ON SURVIVAL OUTCOMES
Authors: Michael Back, Patrick Horsley, Jackie Yim, James Drummond
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND Multifocal glioblastoma(MF-G) are often clustered with presumed uniform worse prognosis. This study explores varying patterns of infiltration of MF-G in relation to radiological features, including presence of contiguous MRI T2-weighted abnormalities and adjacent neural tract pathway involvement. METHODS Consecutive patients with glioblastoma from 2016-2020 managed under EORTC-NCI(Stupp60Gy) Protocol had manual tumour segmentation on T1gd and T2w sequences. Multifocal disease was defined as T1gd or solid T2w-abnormality a minimum of 10mm from the dominant lesion. Number of foci, maximum dimension, cortical/white matter site and distance from dominant lesion were recorded. Presence of contiguous T2w-abnormality was recorded, and correlated to ten major neural tract pathways. Progression-free(PFS) and overall survival(OS) were analysed. RESULTS Forty of 177 patients(23%) were identified with MF-G. These had less near-total resection(p = 0.001), but no difference in ECOG(p = 0.16), or MGMT-methylation(p=0.23). Foci had median size of 14.5mm (q1-3: 10-20); 73% enhancing and 58% solitary. Median distance from dominant lesion was 23mm (q1-3:15-25). Contiguous T2w abnormality and involvement of identified neural tract was evident in 78% and 83% respectively. The multifocal lesion was based in cortex in 33%, and white matter in 67%. Survival outcomes were worse with MF-G: OS (p &amp;lt; 0.01) was 16.0 months (95%CI: 13.6-18.4) versus 19.9 months (95%CI: 17.6-22.2); and PFS (p = 0.01) was 10.8 months (95%CI: 9.9-11.7) versus 13.6 months (95%CI: 11.1-16.1). Improved PFS was associated with larger lesion size(p = 0.04), and cortical lesions(0.04). Those MF-G with contiguous T2w-abnormality(p = 0.06); identified neural tract(p = 0.07) or enhancement(p = 0.08) had trend to worse PFS. MGMT(p = 0.10), ECOG(p = 0.62) and extent of resection(p = 0.07) were not associated with PFS, nor radiological factors of foci number(p = 0.19) and lesion distance(p = 0.16). CONCLUSIONS Radiological pattern of infiltration in MF-G is associated with different natural history. Improved PFS was associated with cortical foci without contiguous T2 abnormality or tract involvement. Recognising infiltration patterns may impact on RT target volume delineation and understanding prognosis.
NIMG-01. PREDICTING POST-STEREOTACTIC RADIOTHERAPY MAGNETIC RESONANCE IMAGE OUTCOMES OF BREAST CANCER METASTASES TO THE BRAIN
Authors: Shraddha Pandey, Tugce Kutuk, Matthew Mills, Mahmoud Abdalah, Olya Stringfield, Kujtim Latifi, Wilfrido Moreno, Kamran Ahmed, Natarajan Raghunand
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND Stereotactic radiosurgery (SRS) is a cornerstone in the management of Breast Cancer Metastases to the Brain (BCMB). While control rates are high following SRS, radiation necrosis is a rare but potentially devastating long-term toxicity. There is a clinical need for automated/semi-automated methods to assess tumor response and optimize the RT plans for local control with minimal long-term toxicity. Multiparametric MRI (mpMRI), particularly Apparent Diffusion Coefficient of water (ADC) maps, contain information that is mechanistically relatable to voxel-level tumor response to RT. We report a deep learning-based approach to predict post-SRS ADC maps, FLAIR, T2-weighted (T2W), T1-weighted unenhanced (T1W) and contrast-enhanced (T1WCE) images, from pre-SRS T1W, T1WCE, T2W and FLAIR images, ADC maps, and the delivered RT dose map. These “forward models” will enable the radiation oncologist to simulate radiologic outcomes and iteratively optimize RT plans for local control with minimal toxicity. METHODS We trained a variant of the pix2pix Generative Adversarial Network (GAN) on MRI and RT dose map data from 18 BCMB patients treated with stereotactic radiation with confirmed controlled and locally recurrent metastases. Patients were treated with stereotactic radiation dose of 1-40 Gy between 2013-2019. RESULTS On test data from 6 BCMB patients, the trained forward model predicted post-SRS ADC values within the Gross Tumor Volume (GTV) that were broadly in agreement with ground truth post-SRS ADC maps. In agreement with expectations, the forward model also predicts increasing post-RT ADC within the GTV with increasing simulated RT doses in the range of 1-71 Gy. We have also explored an inverse model to predict the RT dose map required to produce “prescribed” post-SRS ADC values within the GTV. CONCLUSIONS We envision that the forward models will assist the radiation oncologist in initial RT dose plan optimization, while the inverse model may be useful for daily RT plan optimization.
NIMG-58. IMMUNOPET OF 89ZR-DFO-CD69 AB VISUALIZES T-CELL ACTIVATION AND PREDICTS SURVIVAL FOLLOWING IMMUNOTHERAPY IN MURINE GBM MODEL
Authors: Michal Nisnboym, Sarah Vincze, Itay Raphael, Chaim Sneiderman, Zujian Xiong, Bo Li, Kathryn Day, Joseph Latoche, Jessie Nedrow, Carolyn Anderson, Thomas Pearce, Ian Pollack, Frank Lieberman, Jan Drappatz, Wilson Edwards, Gary Kohanbash
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION Glioblastoma (GBM) is the most malignant brain tumor in adults, with a dismal prognosis despite aggressive therapy. Immunotherapy is currently being evaluated as a treatment modality for recurrent GBM. MRI is not adequate for response assessment to immunotherapy even after using refined response assessment criteria. Thus, there is a need for the development of neuroimaging techniques for response assessment. T-cells are key mediators of cancer immunotherapy responses and upregulation of CD69 is a marker of T-cell activation. Our aim is to use PET/CT imaging to non-invasively quantify CD69 in vivo, following immunotherapy, and correlate the expression to survival. METHODS CD69 was evaluated by flow cytometry and immunofluorescence staining on human and mouse in vitro activated T-cells and on dissociated tumors from GL261 glioma-bearing mice treated with anti-PD1/anti-CTLA4 immunotherapy (ICI). Single-cell RNA sequencing (ScRNAseq) datasets from recurrent GBM patients receiving (n=20) or not receiving (n=22) ICI were examined for CD69 expression on tumor infiltrating lymphocyte (TIL) populations. PET/CT was performed on mice (n=30) receiving radiolabeled anti-CD69 antibody (89Zr-DFO-anti-CD69) to evaluate response to ICI therapy. Standard uptake values (SUV) were compared between ICI and controls and in relationship to survival. RESULTS We confirmed CD69 upregulation upon T-cell activation in vitro. Ex vivo, CD69 expression significantly increased on TILs early after ICI treatment compared to control (63.46% vs 24.37% CD69+/TILs, respectively; p=0.017). ScRNAseq demonstrated significant elevated CD69 expression in almost all TIL populations tested in recurrent GBM patients treated with ICI compared with a control group. ImmunoPET demonstrated significantly higher anti-CD69 tracer uptake in ICI-treated mice compared with controls. Most importantly, we observed a strong positive correlation between survival and immunoPET SUV (r=0.9425, p=0.016) in the ICI-treatment group, but not within the control group. CONCLUSIONS Our study demonstrates the potential incorporation of CD69 ImmunoPET as response assessment to ICI for GBM patients.
EXTH-104. ROLE OF CLPP AND MITOCHONDRIAL METABOLISM IN THE ANTI-CANCER EFFECTS OF IMIPRIDONE ONC201 AND ONC206 IN GLIOBLASTOMA AND DIPG
Authors: Scott Foster, Andrew Lee, Cristina Maranto, Joshua E Allen, Randall Lanier, Phiroze Sethna, Varun V Prabhu
Journal: Neuro-Oncology (2022)

Abstract ONC201 is the first bitopic dopamine receptor D2 (DRD2) antagonist and allosteric mitochondrial protease ClpP agonist. ONC201 is well tolerated and induces durable tumor regressions in H3 K27M-mutant glioma patients. ONC206, a derivative of ONC201 currently in Phase I trials, is also a bitopic DRD2 antagonist and ClpP agonist with enhanced nanomolar potency relative to ONC201. We evaluated in vitro efficacy, mechanism(s) of action and acquired resistance for ONC201 and ONC206 in glioblastoma (GBM) (T98G, A172, U87MG), H3.3 K27M mutant DIPG (SF8628, SF7761) and astrocytoma (H4, U118MG) cell lines. ONC206 was more potent than ONC201 in cell viability assays for all line. A mutation in ClpP has previously been associated with resistance to imipridones. Accordingly, SF8628 cells with a CRISPR-mediated ClpP knockout were resistant to both ONC201 and ONC206. Polyclonal resistant cell lines were generated through prolonged passaging in increasing concentrations of ONC201 (SF8628 and T98G cells) or ONC206 (T98G cells). Cells with acquired resistance to ONC201 (ONC201Res) or ONC206 (ONC206Res) showed cross resistance to both imipridones. Time-stability of resistance was confirmed by removing drug for 2 to 4 weeks and retesting. Whole genome sequencing revealed ClpP mutations in both ONC201Res and ONC206Res T98G cells. RNAseq analysis revealed upregulation of the integrated stress response, apoptosis pathways, and amino acid metabolism with imipridone treatment in T98G parental cells but not resistant clones. Depleting glucose in the media enhanced cell viability inhibition by imipridones, indicating mitochondrial metabolism may contribute to their mechanism of action. Our results identify ClpP and mitochondrial metabolism as key aspects for the mechanism of action of ONC201 and ON206 in DIPG and GBM cell lines.
NCMP-03. HEADACHE IN PATIENTS WITH NON-CNS CANCER
Authors: Bernardo Cacho-Diaz, Oscar Arrieta
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND Almost everybody will experience at least one headache episode and almost 40% of the world-population will be diagnosed with some sort of cancer during their life; nevertheless, their association has scantly been measured. Aim: To identify if headache characteristics and/or accompanying signs were associated with brain metastases (BM) in patients with non-CNS cancer. METHODS Patients with systemic cancer and headache sent for evaluation between June 2012 and June 2018 were included. Hematologic or primary CNS tumors were excluded. Magnetic resonance imaging (MRI) was performed in most; the remaining were followed for at least a year. Logistic regression analyses were used to measure associations. RESULTS From 572 patients with cancer and headache, 216 (38%) were diagnosed with BM. Variables significantly (P &amp;lt; 0.05) associated with BM after multivariable analysis were male gender (OR 1.97), headache starting after cancer diagnosis (OR 21), oppressive type (OR 1.9), presence of vomiting (OR 5.78), not increased by changes in position (OR 2.2), and generalized location (OR 0.34). Having another symptom/sign other than headache was seen in 73% of patients with BM and was significantly associated with a higher risk of BM [OR 6.08 (9%%CI 2.1-17.3)], especially if patients presented with altered mental status (OR 15), visual complaint (OR 15), focal motor weakness (OR 11), seizures (OR 15), ataxia (OR 19), and/or vertigo (OR 3.8). CONCLUSION Headache in patients with cancer should be considered a warning sign, it′s characteristics and accompanying signs should be considered to assess individually the risk of being diagnosed with BM.
CSIG-41. SENSITIZING CANCER CELLS TO TUMOR TREATING FIELDS (TTFIELDS) BY INHIBITION OF PI3K
Authors: Anat Klein-Goldberg, Tali Voloshin, Efrat Zemer-Tov, Rom Paz, Lilach Koren, Kerem Wainer-Katsir, Alexandra Volodin, Bella Koltun, Boris Brant, Yiftah Barsheshet, Tal Kan, Gadi Cohen, Cfir David, Tharwat Haj Khalil, Adi Haber, Moshe Giladi, Uri Weinberg, Yoram Palti
Journal: Neuro-Oncology (2022)

Abstract Tumor Treating Fields (TTFields) are alternating electric fields, which disrupt cellular process critical for cancer cell survival and tumor progression. TTFields therapy is approved for the treatment of glioblastoma (GBM) and unresectable malignant pleural mesothelioma, and is being tested in clinical studies for the treatment of other solid tumors, including ovarian cancer, non-small cell lung carcinoma (NSCLC), and hepatocellular carcinoma (HCC). The current study aimed to detect potential mechanisms that may reduce cellular sensitivity to TTFields, and target these pathways in order to re-sensitize the cells to TTFields. Cancer cells (Ovarian A2780, GBM U-87 MG, and NSCLC H1299) that display reduced sensitivity to TTFields were generated by continuous long-term TTFields application (7 or 13 days, depending on the cell line). A Luminex multiplex assay revealed activation of the PI3K/AKT/mTOR signaling pathway in these cells, with significant increases in phosphorylation levels of AKT and RPS6. This elevation was also observed by immunohistochemistry in tumor sections from N1S1 HCC tumor-bearing rats treated with TTFields relative to sham. Treatment of cells with PI3K inhibitors re-sensitized them to TTFields and downregulated the phosphorylation of AKT. Concomitant application of TTFields with the PI3K inhibitor alpelisib in mice orthotopically implanted with MOSE-L firefly luciferase (FFL) ovarian cancer cells resulted in enhanced efficacy, as determined by In Vivo Imaging System (IVIS) measurements of tumor volume. Overall, this study demonstrated that the PI3K/AKT/mTOR signaling pathway is involved in reduced cancer cell sensitivity to long-term application of TTFields, and that re-sensitization may be achieved with relevant inhibitors. The results provide a rationale for further examining the potential benefit of TTFields concomitant with PI3K inhibitors.
BIOM-58. ROLE OF CD79B Y196 MUTATION IN PCNSL AS A POTENT PREDICTIVE MARKER FOR FAVORABLE RESPONSE TO R-MPV TREATMENT AND DEVELOPMENT OF RAPID ALL-IN-ONE GENOTYPING SYSTEM FOR MOLECULAR MARKERS OF PCNSL
Authors: Junya Yamaguchi, Fumiharu Ohka, Chalise Lushun, Kazuya Motomura, Kosuke Aoki, Kazuhito Takeuchi, Yuichi Nagata, Satoshi Ito, Nobuhiko Mizutani, Masasuke Ohno, Noriyuki Suzaki, Syuntaro Takasu, Yukio Seki, Kuniaki Tanahashi, Masaki Hirano, Hiroyuki Shimizu, Yotaro Kitano, Sachi Maeda, Shintaro Yamazaki, Toshihiko Wakabayashi, Yutaka Kondo, Ryuta Saito
Journal: Neuro-Oncology (2022)

Abstract Although high-dose methotrexate (HD-MTX)-based chemotherapy, such as rituximab, HD-MTX, procarbazine and vincristine (R-MPV) regimen, has significantly prolonged the survival of patients with primary central nervous system lymphoma (PCNSL), predictive factors for response to R-MPV have not yet been investigated. Then, we investigated the correlation of MYD88 L265P and CD79B Y196 mutations, which are the most frequently found molecular alterations in PCNSL, with prognosis of patients with PCNSL treated with R-MPV. 47 and 21 patients with PCNSL treated with R-MPV and HD-MTX respectively were included, and correlation of their MYD88 and CD79B status with prognosis was analyzed. R-MPV achieved an excellent tumor control rate (61.6% and 69.9% of 5-year progression-free and overall survival rates, respectively). Among the 47 patients, 36 harbored MYD88 L265P or CD79B Y196 mutations. While the MYD88 L265P mutation had no significant effect on survival, patients with CD79B Y196 mutations exhibited prolonged survival (P &amp;lt; 0.05). However, the association of the CD79B Y196 mutation with a better prognosis was not observed in the HD-MTX cohort, which indicated that the CD79B Y196 mutation was a predictive marker for a favorable response to R-MPV. Furthermore, we established an all-in-one rapid genotyping system for these genetic mutations. This system enabled the detection of these genetic mutations in a small amount of biopsy samples within 90 min. In conclusion, we revealed that the CD79B Y196 mutation is associated with a good response to R-MPV, and the rapid and accurate genotyping system for MYD88 L265P and CD79B Y196 mutations that we developed in this study will enable reliable rapid molecular diagnosis and early prediction of response to R-MPV, which might help to determine the best treatment strategy for PCNSL.
NCOG-09. RADIATION INDUCED CEREBRAL VOLUME LOSS AND CEREBROVASCULAR DISEASE RISK IN SURVIVORS OF GRADE 2 AND 3 GLIOMAS
Authors: Melissa Gardner, Sebastian Winter, Jorg Dietrich, Elizabeth Gerstner, Janet Sherman, Helen Shih, Michael Parsons
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION Cranial irradiation with protons (PRT) as compared with photons (PHT) reduces radiation exposure to healthy brain tissue and may mitigate early- and late-delayed complications. Prior work in our group has demonstrated that PRT results in less brain atrophy over 2 years post-treatment as compared with PHT. It is unknown whether individual factors, such as cerebrovascular disease risk (CVDR; known to be important in post-RT brain changes), interacts with treatment type to affect brain volume change. METHODS Patients treated with PRT for grade 2 or 3 gliomas were meticulously matched to patients treated with PHT using an eleven-tiered criterion (i.e., age, sex, tumor type, tumor location, laterality, IDH mutation status, 1p19q deletion status, concurrent chemotherapy, adjuvant chemotherapy, total Gy dose, and number of fractions). Brain volume changes were evaluated by measuring changes in ventricular size in the contralesional hemisphere (to reduce impact of tumor-related changes on volumetric measurements). A CVDR score was created, incorporating history of hypertension, hyperlipidemia, smoking, and diabetes. Correlation and multiple regression analyses examined the relationship between CVDR and brain volume loss over 2 years. RESULTS Mann-Whitney tests of independence showed no significant differences in CDVR between PHT and PRT treatment groups. Cerebral volume loss correlated significantly with CVDR (r =.404, p =0.02) and treatment type (r=-.366, p =0.036). Age and gender were unrelated to volume loss. A multiple regression analysis that included treatment type (PHT, PRT) and CVDR accounted for 23% of the variance in volume loss, F(2, 32) = 4.383, p &amp;lt; .021. CONCLUSION The current study demonstrates that neurotoxicity of radiation therapy is related to both CVDR and radiation treatment type. Longitudinal data, including a larger sample size, are warranted to confirm these preliminary findings. Inclusion of routine neuropsychological outcome data will be critical to understand the functional significance of these results.
CTNI-61. CLINICAL EFFICACY AND PREDICTIVE BIOMARKERS OF ONC201 IN H3K27M-MUTANT DIFFUSE MIDLINE GLIOMA
Authors: Abed Rahman Kawakibi, Rohinton Tarapore, Sharon Gardner, Andrew Chi, Sylvia Kurz, Patrick Y Wen, Isabel Arrillaga-Romany, Tracy Batchelor, Nicholas Butowski, Ashley Sumrall, Nicole Shonka, Rebecca Harrison, John DeGroot, Minesh Mehta, Yazmin Odia, Matthew Hall, Doured Daghistani, Timothy Cloughesy, Benjamin Ellingson, Michelle Kim, Yoshie Umemura, Hugh Garton, Andrea Franson, Jonathan Schwartz, Sunjong Li, Rodrigo Cartaxo, Karthik Ravi, Evan Cantor, Jessica Cummings, Alyssa Paul, Dustin Walling, Matthew Dun, Jason Cain, Jiang Li, Mariella Filbin, Lili Zhao, Chandan Kumar-Sinha, Rajen Mody, Arul Chinnaiyan, Ryo Kurokawa, Drew Pratt, Sriram Venneti, Jacques Grill, Cassie Kline, Sabine Mueller, Adam C Resnick, Javad Nazarian, Sebastian Waszak, Joshua E Allen, Carl Koschmann
Journal: Neuro-Oncology (2022)

Abstract Patients with H3K27M-mutated diffuse midline glioma (DMG) have no proven effective therapies beyond radiation. ONC201, a DRD2 antagonist and mitochondrial ClpP agonist, has shown promise in this population. Clinical and genetic variables associated with ONC201 response in H3K27M-mutant DMG continue to be investigated. A combined clinical and genetic study evaluated patients with H3K27M-DMG treated with single-agent ONC201 at the established phase 2 dose. Clinical outcomes of patients treated on two recently completed multi-site clinical studies (NCT03416530 and NCT03134131, n = 75) were compared with historical control data from patients with confirmed H3K27M-DMG (n = 391 total, n = 119 recurrent). Patients treated with ONC201 monotherapy following initial radiation, but prior to recurrence, demonstrated a median overall survival (OS) of 25.6 months from diagnosis and recurrent patients demonstrated a median OS of 16.2 months from recurrence, both of these more than doubling historical outcomes. Using a Cox model to correct for age, gender and tumor location, OS of ONC201-treated patients with H3K27M-mutant tumors remained significantly better than non-ONC201-treated historical controls (p = 0.0001). A survival and radiographic analysis based on tumor location, revealed stronger responses in thalamic patients. In patients with thalamic tumors treated after initial radiation (n = 16), median OS was not reached with median follow up of 22.1 months (historical control median OS of 12.5 months, n = 83, p = 0.0001). Significant correlations were found between baseline cerebral blood flow (CBF) on perfusion imaging and OS (Pearson’s r = 0.75, p = 0.003) and between nrCBF and PFS (r = 0.77, p = 0.002). Baseline tumor sequencing from treated patients (n = 20) demonstrates EGFR mutation (n = 3) and high EGFR expression as a marker of resistance and improved response in tumors with MAPK-pathway alterations (n = 5). In conclusion, ONC201 demonstrates unprecedented clinical and radiographic efficacy in H3K27M-mutant DMG with outcomes enriched in patients with thalamic tumors, treatment prior to recurrence, MAPK-pathway alterations, and patients with relatively high CBF.
CTNI-06. IMPROVING INSOMNIA IN PATIENTS WITH PRIMARY BRAIN TUMORS USING COGNITIVE BEHAVIORAL THERAPY: RESULTS FROM AN NRG NCORP PILOT TRIAL
Authors: Ashlee Loughan, Autumn Lanoye, Kelcie Willis, Amber Fox, Alicia Zukas, Scott Ravyts
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND Sleep disturbance is among the most common symptoms endorsed by patients with primary brain tumor (PwPBT), with many reporting clinically-elevated insomnia and poor management of sleep-related symptoms by their medical team. Though Cognitive Behavioral Therapy for Insomnia (CBT-I) remains the front-line treatment for sleep disturbance, CBT-I has yet to be evaluated in PwPBT. METHODS PwPBT were recruited locally by direct referral and fliers, and nationally by social media support group postings. Forty PwPBT and insomnia enrolled in a six-week group-based telehealth CBT-I phase IIa single-arm proof-of-concept trial: 50.0% female, 68.2% non-Hispanic white, 55.0% high-grade, 42.5% oligodendroglioma, Mage = 52.4 (SD = 12.0, range 31-77). Participants completed data collection at baseline and post-intervention. Self-report measures assessed insomnia (ISI), fatigue (BFI), mood (PHQ-9, GAD-7) and quality-of-life (QLQ-30). Cognitive assessment included measures of attention (WAIS-IV Digits, TMT), verbal fluency (COWAT) and memory (HVLT). Intervention effects for self-report outcomes were analyzed using paired t-tests; effects for cognitive outcomes were analyzed using repeated-measures ANCOVA controlling for age. RESULTS Among those with complete data (n=34), significant improvements were identified for insomnia (t(33) = 8.6, p &amp;lt; .001, Cohen’s d = 1.5) and fatigue (t(30) = 4.7, p &amp;lt; .001, Cohen’s d = 0.8) symptoms. Depression (t(33) = 5.2, p &amp;lt; .001, Cohen’s d = 0.9) and anxiety symptoms (t(33) = 4.2, p &amp;lt; .001, Cohen’s d = 0.7) also improved. Quality-of-life improved with respect to role (t(33) = 2.8, p = .01, Cohen’s d = 0.5), emotional (t(33) = 2.8, p = .01, Cohen’s d = 0.5), cognitive (t(33) = 3.9, p &amp;lt; .001, Cohen’s d = 0.7), and social functioning (t(33) = 3.5, p = .001, Cohen’s d = 0.6)—but not physical functioning (t(33) = 0.5, p = .60, Cohen’s d = 0.1). No clinically or statistically significant cognitive changes were found. CONCLUSION This trial is the first to preliminarily assess efficacy of CBT-I, a non-pharmacological treatment for insomnia, in PwPBT. Results suggest promising benefit of CBT-I in insomnia severity, fatigue, mood, and most quality-of-life indices for individuals challenged by PBT and insomnia. These findings support further study in a scientifically rigorous phase IIb randomized feasibility trial.